Overexpression of PKC, a cytoplasmic serine/threonine kinase involved in signal transduction, may promote the development and maintenance of tumors. We have previously reported safety and activity of ISIS 3521 at 2.0 mg/kg by a 21 day CI. The present study explored an alternate schedule of 24 hr CI once weekly. Between 1/98-11/98, 11 patients with refractory solid tumors received ISIS 3521 at doses of 6, 12, 18 and 24 mg/kg in cohorts of 3 to six. 91 doses have been delivered so far. No gr 4 toxicities occurred. Gr 3 toxicities were: fever/chills (n =1) and hemorrhage (n =1) at 18 mg/kg and chills (n =1) at 24 mg/kg. Other gr 1/2 toxicities include thrombocytopenia (4), myalgias (6), chills (7), headache (3), fatigue (4), fever (7) and nausea/vomiting (4) which were transient. Steady state plasma levels were achieved within 4 hr and were proportional to increasing dose. Primate studies had identified complement activation as a potential toxicity of ISIS 3521; therefore, split products (C3a and Bb) were analyzed in all patients. Transient activation was seen at doses > 18 mg/kg when compared to < 18 mg/kg (median 3.9 versus 1.4- fold increase in C3a, p<0.001 and median 1.9 versus 1.0- fold increase in Bb, p<0.001). This correlated with a 1.5 second prolongation of prothrombin time (p<0.001) but not with grade 1-2 thrombocytopenia. Clinical evidence of complement activation was not observed. One patient had stable colon cancer for 3+ months. This regimen appears acceptable and patient accrual is currently ongoing to determine the MTD.